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Biomedical subjects

G Hardy

Publications and source records attributed to G Hardy.

At least 37 records · Page 2Linked to original sources
PubMed2001

Development of immunotherapeutic strategies for HIV-1.

In the majority of untreated patients, HIV-1 infection presents as a progressive disease of the immune system. Recent studies indicate that immune responses can be induced in HIV-1 infected individuals, leading to some immune control of virus replication. Such immune responses are also observed in small numbers of untreated HIV-1 infected long-term non-progressor (LTNP) patients, as well as in other viral infections (including those with human herpes viruses). Emerging novel technologies, animal studies and detailed immunological studies have proven invaluable in defining the immune responses that are associated with a favourable clinical outcome. Central effector and regulatory cells are HIV-1-specific CD8+ cytotoxic T-lymphocytes (CTL) and CD4+ helper T-lymphocytes respectively. Fully functional antigen-presenting cells (APC) are also essential in all stages of HIV-1 infection and possibly some (but not all) antibody responses contribute to beneficial immunity. The availability of combination anti-retroviral drug therapy, which successfully controls viraemia, has enabled a beneficial outcome in many HIV-1 infected individuals. Since no chronically HIV-1 infected patient has been shown to eradicate virus, novel approaches utilising therapeutic immunisation and various cytokines to manipulate immune responses and to induce and steer immunity towards a desired phenotype are required. There is a clear rationale for immunotherapeutic intervention in chronic progressive HIV-1 infection, which forms the foundation for novel approaches aimed at inducing and maintaining immune control. Here we review the immunopathogenesis of HIV-1 infection and discuss the promises of therapeutic immunisation and immunotherapy in general and their potential in the treatment of chronic HIV-1 disease.

Animals↗
PubMed2000

Deep and stable interferometric nulling of broadband light with implications for observing planets around nearby stars

The number of indirectly detected planetary systems around nearby stars has grown tremendously since their initial discovery five years ago. But the direct observation of light reflected from these systems remains a formidable task, because of the high contrast ratios between them and their parent stars, and because of the tiny angular separations. Theoretically, these difficulties can be overcome by using a dual-aperture stellar interferometer in which the starlight is cancelled, or 'nulled' by broadband destructive interference, leaving the planet's light visible. Although the basic requirement of equal and oppositely directed electric fields is easy to state, an experimental demonstration of deep broadband nulling has been lacking, owing to difficulties engendered by the needs for extreme symmetry and stability, and low dispersion in the optical system. Here we report the deep (10(-4)) and stable nulling of broadband (18% bandwidth) thermal light. These results validate the physical principles underlying future planet-searching interferometers, and our laboratory instrument will serve as a prototype for the nulling instrument to be implemented on the Keck interferometer in 2001.

Journal Article↗
PubMed2000

Cyclosporine A and cremophor EL induce contractions of human saphenous vein: involvement of thromboxane A2 receptor-dependent pathway.

Chronic treatment with Sandimmune (cyclosporine A [CsA] dissolved in Cremophor EL [CrEL]) is often associated with hypertension and nephrotoxicity. The aims of the present study were to assess the effect of Sandimmune and its two main components (CsA and CrEL) on human saphenous veins and to study the underlying mechanism of their contractile responses. In organ bath, concentration-response curves for Sandimmune (36 ng/ml-120 microg/ml of CsA). CsA (36 ng/ml-120 microg/ml), or CrEL (2.4 microg/ml-8 mg/ml) were elicited in the presence of a thromboxane A2 (TXA2) receptor antagonist (GR32191, 0.3 microM), a cyclooxygenase inhibitor (indomethacin, 1 microM), a 5-lipoxygenase inhibitor (AA861, 10 microM), or their respective vehicles. In addition, the production of TXA2 after CsA challenge was assessed by enzyme immunoassay. Sandimmune, CsA, and CrEL induced concentration-dependent contractions on human saphenous veins. In terms of potency, CsA was a more potent vasoconstrictor agent than CrEL (EC50 values: 11.9+/-3.7 microg/ml (CsA, n = 12) vs. 1.2+/-0.4 mg/ml (CrEL, n = 16), p < 0.05). In contrast, in terms of efficacy, CrEL induced greater contractions than CsA (Emax (% of KCl 90 mM-induced contraction): 98.1+/-16.1% (CrEL, n = 16) vs. 17.0+/-4.3% (CsA, n = 12) p < 0.05). Pretreatment with GR32191 significantly reduced by 85% and 56% the contractions elicited by CsA and CrEL, respectively, whereas indomethacin had no effect. Finally, CsA (12 and 120 microg/ml) failed to stimulate TXA2 production. These in vitro data suggest that Sandimmune-induced contractions on human vascular smooth muscle appear to be mediated by CsA in the therapeutic ranges of doses and by both CsA and CrEL, which, in supratherapeutic doses, acted through a TXA2 receptor-dependent pathway.

Biphenyl Compounds↗
PubMed2000

Assessing adult attachment status with clinically-orientated interviews: a brief report.

The object of this study was to examine the possibility of using clinically-orientated interviews to gain a similar attachment classification to the Adult Attachment Interview. Little agreement on classifications was shown between the two interviews, showing insufficient evidence to suggest that it is possible to assess adult attachment status using clinically-orientated interviews.

Adult↗
PubMed2000

[Bromide poisoning and false hyperchloremia].

A 36-year-old female patient was admitted at three different times for neuropsychiatric disorders. No diagnoses were made during the first two hospital stays. A pseudohyperchloraemia allowed the diagnosis of bromide poisoning during her third hospital stay. Chloraemia was measured over 16 days by potentiometric, colorimetric and coulometric methods, in order to assess the analytical interferences caused by bromides. Results are reported and discussed. Bromide poisoning was treated by saline diuresis.

Adult↗
PubMed2000

Spatial and temporal localisation of bone morphogenetic protein-3 (osteogenin) in the developing rat submandibular gland.

Submandibular gland morphogenesis is a highly regulated process modulated by epithelio-mesenchymal interactions. Bone morphogenetic proteins (BMPs), members of the transforming growth factor-beta (TGF-beta) superfamily, are known to be soluble mediators of epithelio-mesenchymal interactions during the development of certain organs. The aim of this study was to localise bone morphogenetic protein-3 (BMP-3 or osteogenin), spatially and temporally in the developing rat submandibular gland. Immunocytochemistry was performed on sections of the developing submandibular gland (gestation ages E14.5-E19.5). BMP-3 was localised in the extra-cellular matrix of the mesenchyme of the gland in all the stages examined. Intense staining of BMP-3 was observed in the epithelial cells of the developing end-buds between stages E14.5 and E16.5. As cytodifferentiation progressed (stage E17.5 onwards) the number of epithelial cells in the developing acini in which BMP-3 was present became markedly reduced. Similarly, the number of cells containing BMP-3 in the developing ducts decreased as duct development progressed. By stage E19.5, BMP-3 was located mainly in the immature ducts. While the effects of BMP-3 on matrix macromolecules could not be deduced from this study, its spatial and temporal location within the developing glands may indicate a role in the co-ordinated regulation of branching morphogenesis.

Animals↗
PubMed1999

Technical aspects of trace element supplementation.

Routine supplementation of total parenteral nutrition mixtures with the readily available single or combination trace elements products is becoming more widespread. As more is learned about deficiency syndromes and monitoring techniques, so too must we understand more about the physicochemical interactions between individual trace elements and other nutrients, that could ultimately affect bioavailability. Expert pharmaceutical assessment of these complex reactions, that have been demonstrated to occur in solution, becomes increasingly important in order to optimize the efficacy of micronutrient therapy.

Dietary Supplements↗
PubMed1999

Therapeutic vaccines in HIV.1 infection.

In this review we address questions which must be considered if better attempts are to be made to treat all persons presently infected with human immunodeficiency virus (HIV). There are thirty million people in the world presently living with HIV, only 10% of whom are likely to be able to access currently available drug therapy. Even when available, such therapy causes considerable inconvenience and undesirable clinical side effects, and fails to eradicate virus from a small reservoir of latently infected cells. Thus, we must ask what forms of alternative therapy might be used. One strategy that may be considered is to reduce virus levels as low as possible using highly active antiretroviral therapy (HAART), followed by modulation of host immunity with immunotherapy in order to effect an appropriate and efficient response mimicking that found in long-term asymptomatic patients, with the aim of indefinitely maintaining the asymptomatic period following discontinuation of chemotherapy, or even of eradicating the virus from the latent reservoirs. In 1987, long before the advent of highly active antiretroviral therapy, J. Salk proposed the use of a 'suitable potent non-infectious (HIV) immunogen' to delay or prevent the development of AIDS in infected individuals (1). The objective of administering such an agent was to 'enhance and prolong the presence of (immunologically) protective factors'. The stated aim at that time was 'to destroy virus and viral antigen producing cells by the induction of the immune system's cytotoxic mechanisms known to rid the host of virus and virus producing cells'. Twelve years later, and after a quarter of a century living with HIV, and with the advent of HAART, is it time to use our knowledge of the host's own immune system to fight this seemingly intractable invader?

AIDS Vaccines↗
PubMed1999

GP referrals to adult psychological services: a research agenda for promoting needs-led practice through the involvement of mental health clinicians.

General practitioners' responses to psychological problems presented in the surgery have a significant impact on the care that their patients will receive. Importantly, their referral behaviour has a knock-on effect on the shaping of psychological treatment services. The present paper summarizes the types of influences that impact on GPs' referral decisions and investigates the possible role that mental health clinicians may play in facilitating these processes. GPs' referral decisions are shown to be affected by a large number of factors which fall within the following domains: patients' help-seeking behaviour and their representations of mental ill-health; the ability of GPs to detect psychological disorders; GPs' attitudes towards psychological problems and their management; service criteria for appropriate referral; and links with mental health services. For each of these domains, methods by which mental health clinicians can promote better referral practice are suggested. Recommendations are made for further research into the efficacy and clinical utility of these methods.

Adult↗
PubMed1998

The influence of amino acid source on the stability of ascorbic acid in TPN mixtures.

This study was undertaken to investigate the stability of ascorbic acid and its primary degradation product, dehydroascorbic acid, in total parenteral nutrition (TPN) mixtures. The influence of the type of bag and the commercial source of amino acid on ascorbate degradation was examined, using a stability-indicating high-pressure liquid chromatography (HPLC) method. Ascorbic acid was most stable in multilayered bags, compared with ethylvinyl acetate (EVA) bags. Results indicated that, in multilayered bags, the initial rapid ascorbic acid degradation was greatest in TPN mixtures containing amino acid infusions without reducing activity. In contrast, degradation in TPN mixtures containing amino acids with reducing compounds (Vamin 14 and Freamine III 8.5%) was less than 10% of the added amount. Dehydroascorbic acid degraded approximately in parallel with ascorbic acid, and it contributed to the total available ascorbate activity. The addition of air to TPN mixtures in multilayered bags caused accelerated degradation of both ascorbic acid and dehydroascorbic acid. It is concluded that TPN mixtures compounded in multilayered bags can be safely assigned extended shelf lives, especially if compounded using an amino acid with reducing activity. This is principally due to the protective effect of the bag wall in preventing oxygen transmission, the cause of ascorbic acid oxidation, because oxygen transmission through the bag wall is minimized during storage. TPN mixtures stored in EVA bags should be administered within 2-4 d of compounding, depending on the amino acid infusion used.

Air↗
PubMed1998

Basic principles for compounding all-in-one parenteral nutrition admixtures.

Parenteral nutrition admixtures are complex pharmaceutical entities. The more closely they are examined, the more physico-chemical interactions emerge that could potentially affect stability. The move towards large scale hospital or commercial preparation, with a requirement for extended shelf life, and the increasing use of admixtures as vehicles for drugs and pharmaconutrients have created new formulation challenges for pharmaceutical scientists.

Chemical Phenomena↗
PubMed1998

[Possibilities for revascularization in early and late stage lunate malacia].

There are various biomechanical procedures for the treatment of lunate necrosis in the literature, but only a few deal with the possible revascularisation of the bone. We used the second dorsal metacarpal vascular bundle implantation technique in different stages of Kienböck's disease. Since 1990, twelve patients were treated by this method. In stage I-II according to Lichtman, we implanted the vessels in the lunate after excochleation and cancellous bone grafting, in stage III we used a modified form of the Graner operation and revascularised the proximalised part of the capitate. In the first group, six patients, we observed significant improvement in five cases clinically, radiologically confirmed stagnation of the process in four cases. In the second group of six patients, the clinical symptoms improved in four cases, three patients had to change work and one patient developed a pseudarthrosis between the capitate and corticocancellous block, but the proximalised part of capitate survived in all cases. Vascular bundle implantation can be a helpful method in early stages of lunate necrosis, helping to slow or to stop the progression of the disease.

Adolescent↗
PubMed1998

The myoepithelium of human major salivary glands revisited.

The presence of myoepithelial cells in salivary glands is of importance with regard to tumour histogenesis, yet there is no consensus in the literature as to the specific location of these cells. A major problem has been the methods of precise identification of myoepithelium at the light microscopic level. The present study therefore reviews the distribution of myoepithelial cells in the major salivary glands (parotid, submandibular and sublingual) of the human, utilising a monoclonal antibody specific to actin, a cytoplasmic component of the myoepithelial cell. Qualitative analysis was performed to assess the distribution of these cells in mucous and serous acini and in the different regions of the ductal system. As previously described, myoepithelial cells were found to be present around serous and mucous acini as well as the intercalated ducts of all the major glands. They appeared to be more abundant in mucous than in serous acini of the submandibular and sublingual glands. In addition, this study has demonstrated the presence of myoepithelial cells in the proximal portion of striated ducts in the submandibular gland--a location that has not previously been reported in the human.

Cell Transformation, Neoplastic↗